Towards spatially selective efferent neuromodulation: anatomical and functional organization of cardiac fibres in the porcine cervical vagus nerve.

Spatially selective vagus nerve stimulation (sVNS) offers a promising approach for addressing heart disease with enhanced precision. Despite its therapeutic potential, VNS is limited by off-target effects and the need for time-consuming titration. Our research aimed to determine the spatial organization of cardiac afferent and efferent fibres within the vagus nerve of pigs to achieve targeted neuromodulation. Using trial-and-error sVNS in vivo and ex vivo micro-computed tomography fascicle tracing, we found significant spatial separation between cardiac afferent and cardiac efferent fibres at the mid-cervical level and they were localized on average on opposite sides of the nerve cross-section. This was consistent between both in vivo and ex vivo methods. Specifically, cardiac afferent fibres were located near pulmonary fibres, consistent with findings of cardiopulmonary convergent circuits and, notably, cardiac efferent fascicles were exclusive. These cardiac efferent regions were located in close proximity to the recurrent laryngeal regions. This is consistent with the roughly equitable spread across the nerve of the afferent and efferent fibres. Our study demonstrated that targeted neuromodulation via sVNS could achieve scalable heart rate decreases without eliciting cardiac afferent-related reflexes; this is desirable for reducing sympathetic overactivation associated with heart disease. These findings indicate that understanding the spatial organization of cardiac-related fibres within the vagus nerve can lead to more precise and effective VNS therapy, minimizing off-target effects and potentially mitigating the need for titration. KEY POINTS: Spatially selective vagus nerve stimulation (sVNS) presents a promising approach for addressing chronic heart disease with enhanced precision. Our study reveals significant spatial separation between cardiac afferent and efferent fibres in the vagus nerve, particularly at the mid-cervical level. Utilizing trial-and-error sVNS in vivo and micro-computed tomography fascicle tracing, we demonstrate the potential for targeted neuromodulation, achieving therapeutic effects such as scalable heart rate decrease without stimulating cardiac afferent-related reflexes. This spatial understanding opens avenues for more effective VNS therapy, minimizing off-target effects and potentially eliminating the need for titration, thereby expediting therapeutic outcomes in myocardial infarction and related conditions.

Defining the Cross-Volume Effect of Extracorporeal Life Support on Outcomes of Cardiogenic Shock.

BACKGROUND: Cardiogenic shock (CS) remains a leading cause of mortality despite advancements in mechanical circulatory support and other management strategies. In particular, venoarterial extracorporeal membrane oxygenation (ECMO) requires expertise in cardiac surgery, cardiology, and critical care. The benefits of such expertise may extend beyond ECMO patients. METHODS: Adult (≥18 years) hospitalizations with a primary diagnosis of CS, not undergoing ECMO, cardiac operations, durable LVAD, or transplantation, were abstracted from the 2016-2020 Nationwide Readmissions Database. Multivariable regression models were developed to assess the association of cardiac surgical and ECMO institutional caseload with clinical and financial outcomes. RESULTS: Of an estimated 70,339 patients with CS identified for study, 33,643 (47.8%) were treated at a high-volume hospital for ECMO (HVH-ECMO). HVH-ECMO was associated with decreased odds of in-hospital mortality (AOR 0.85, CI 0.75 - 0.95), respiratory complications (AOR 0.86, CI 0.79 - 0.94), and non-home discharge (AOR 0.86, CI 0.79 - 0.94). However, HVH-ECMO was associated with greater LOS by 1.7 days (CI 1.3 - 2.1) and inpatient costs by $9,170 (CI $6,490 - $12,060). While ECMO volume was inversely associated with the predicted risk of in-hospital mortality, institutional volume of cardiac operations was not significantly associated with mortality. CONCLUSIONS: Our findings suggest improved outcomes for CS patients treated at a HVH-ECMO. Multidisciplinary care pathways, including those among surgery, cardiology, and critical care, may influence CS management. Further studies are needed to characterize long-term outcomes of regionalization and ensure equitable access for all populations.

National trends and outcomes of robotic emergency general surgery in the United States.

BACKGROUND: Robot-assisted surgery has seen exponential adoption over the last decade. Although the safety and efficacy of robotic surgery in the elective setting have been demonstrated, data regarding robotic emergency general surgery remains sparse. METHODS: All adults undergoing non-elective appendectomy, cholecystectomy, small or large bowel resection, perforated ulcer repair, or lysis of adhesions were identified in the 2008 to 2020 National Inpatient Sample. Temporal trends were analyzed using a rank-based, non-parametric test developed by Cuzick (nptrend). Using laparoscopy as a reference, multivariable regressions were used to evaluate the association between robotic techniques and in-hospital mortality, major complications, and resource use for each emergency general surgery operation. RESULTS: Of an estimated 4,040,555 patients undergoing emergency general surgery, 65,853 (1.6%) were performed using robotic techniques. The robotic proportion of minimally invasive emergency general surgery increased significantly overall, with the largest growth seen in robot-assisted large bowel resections and perforated ulcer repairs. After adjustment for various patient and hospital-level factors, robot-assisted large bowel resection (adjusted odds ratio 0.73, 95% confidence interval 0.58-0.91) and cholecystectomy (adjusted odds ratio 0.66, 95% confidence interval 0.55-0.81) were associated with significantly reduced odds of perioperative blood transfusion compared to traditional laparoscopy. Although robotic techniques were associated with modest reductions in postoperative length of stay, costs were uniformly higher by increments of up to $4,900. CONCLUSION: Robotic surgery appears to be a safe and effective adjunct to laparoscopy in minimally invasive emergency general surgery, although comparable cost-effectiveness has yet to be realized. Increasing use of robotic techniques in emergency general surgery may be attributable in part to reduced complications, including blood loss, in certain operative contexts.

Clinical Outcomes and Resource Utilization in Patients With Peripheral Arterial Disease Hospitalized for Acute Coronary Syndrome.

Previous studies have shown an association between acute limb ischemia and higher mortality in patients with acute myocardial infarction. Although peripheral artery disease (PAD) is a well-known risk factor for development of macrovascular pathology, the effect of its severity is not well investigated in patients hospitalized for acute coronary syndrome (ACS). Using a national cohort of patients with various degrees of PAD, we investigated in-hospital outcomes in patients who were admitted for ACS. Using the 2016 to 2020 Nationwide Readmissions Database, we queried all patients who were hospitalized for ACS (unstable angina, non-ST-elevation myocardial infarction, and ST-elevation myocardial infarction). Patients were further divided into 3 groups, either no PAD (non-PAD), PAD, or critical limb ischemia (CLI). Multivariable models were designed to adjust for patient and hospital factors and examine the association between ACS and PAD severity. Of approximately 3,834,181 hospitalizations for ACS, 6.4% had PAD, 0.2% had CLI, and all others were non-PAD. After risk adjustment, in-hospital mortality was higher by 24% in PAD (adjusted odds ratio 1.24, 95% confidence interval [CI] 1.21 to 1.28) and 86% in CLI (adjusted odds ratio 1.86, 95% CI 1.62 to 2.09) compared with non-PAD. Furthermore, PAD and CLI were linked to 1.23-fold (95% CI 1.20 to 1.26) and 1.67-fold (95% CI 1.45 to 1.86) greater odds of cardiogenic shock compared with non-PAD. Additionally, PAD and CLI were linked with higher odds of mechanical circulatory support usage, cardiac arrest and acute kidney injury compared with non-PAD. Lastly, duration of hospital stay, hospitalization costs and odds of non-home discharge and 30-day readmissions were greater in patients with PAD and CLI compared with non-PAD. PAD severity was associated with worse clinical outcomes in patients with ACS, including in-hospital mortality and resource utilization.

Development and preliminary assessment of a machine learning model to predict myocardial infarction and cardiac arrest after major operations.

INTRODUCTION: Accurate prediction of complications often informs shared decision-making. Derived over 10 years ago to enhance prediction of intra/post-operative myocardial infarction and cardiac arrest (MI/CA), the Gupta score has been criticized for unreliable calibration and inclusion of a wide spectrum of unrelated operations. In the present study, we developed a novel machine learning (ML) model to estimate perioperative risk of MI/CA and compared it to the Gupta score. METHODS: Patients undergoing major operations were identified from the 2016-2020 ACS-NSQIP. The Gupta score was calculated for each patient, and a novel ML model was developed to predict MI/CA using ACS NSQIP-provided data fields as covariates. Discrimination (C-statistic) and calibration (Brier score) of the ML model were compared to the existing Gupta score within the entire cohort and across operative subgroups. RESULTS: Of 2,473,487 patients included for analysis, 25,177 (1.0%) experienced MI/CA (55.2% MI, 39.1% CA, 5.6% MI and CA). The ML model, which was fit using a randomly selected training cohort, exhibited higher discrimination within the testing dataset compared to the Gupta score (C-statistic 0.84 vs 0.80, p < 0.001). Furthermore, the ML model had significantly better calibration in the entire cohort (Brier score 0.0097 vs 0.0100). Model performance was markedly improved among patients undergoing thoracic, aortic, peripheral vascular and foregut surgery. CONCLUSIONS: The present ML model outperformed the Gupta score in the prognostication of MI/CA across a heterogenous range of operations. Given the growing integration of ML into healthcare, such models may be readily incorporated into clinical practice and guide benchmarking efforts.

Association of prior bariatric surgery with outcomes following emergency general surgery.

BACKGROUND: Despite the favorable outcomes and safety profile associated with metabolic and bariatric surgery (MBS), complications may occur postoperatively, necessitating emergency general surgery (EGS) intervention. OBJECTIVES: To evaluate the association of outcomes in patients with prior MBS following EGS interventions. SETTING: Academic, University-affiliated; USA. METHODS: All adults undergoing nonelective EGS operations were identified using the 2016 to 2020 Nationwide Readmission Database. Patients with a history of MBS were subsequently categorized as Bariatric, with the remainder of patients as NonBariatric. The primary outcome of interest was in-hospital mortality, while perioperative complications, length of stay (LOS), hospitalization costs, non-home discharge, and 30-day readmission were secondarily assessed. Multivariable regression models were developed to evaluate the association of history of MBS with outcomes of interest. RESULTS: Of an estimated 632,375 hospitalizations for EGS operations, 29,112 (4.6%) had a history of MBS. Compared to Nonbariatric, Bariatric were younger, more frequently female and more commonly had severe obesity. Following risk adjustment, Bariatric had significantly lower odds of in-hospital mortality (AOR .83, 95%CI .71-.98). Compared to others, Bariatric had reduced LOS by .5 days (95%CI .4-.7) and hospitalization costs by $1600 (95%CI $900-2100). Patients with prior MBS had reduced odds of nonhome discharge (AOR .89, 95%CI .85-.93) and increased likelihood of 30-day readmissions (AOR 2.32, 95%CI 1.93--2.79) following EGS. CONCLUSIONS: Prior MBS is associated with decreased mortality and perioperative complications as well as reduced resource utilization in select EGS procedures. Our findings suggest that patients with a history of MBS can be managed effectively by acute surgical interventions.

Prior bariatric surgery is associated with lower mortality and resource utilization following small bowel obstruction.

Background: Small bowel obstruction (SBO) is a complication of bariatric surgery. However, outcomes of surgical intervention for SBO among patients with prior bariatric surgery remain ill-defined. We used a nationally representative cohort to characterize the outcomes of the SBO management approach in patients with a prior bariatric operation. Methods: All adult hospitalizations for SBO were tabulated from the 2018-2020 National Readmissions Database. Patients with a prior history of bariatric surgery comprised the Bariatric cohort (others: Non-Bariatric). Multivariable models were subsequently developed to evaluate the association of prior bariatric surgery with outcomes of interest. Results: Of an estimated 299,983 hospitalizations for SBO, 15,788 (5.3 %) had a history of prior bariatric surgery. Compared to Non-Bariatric, Bariatric patients were younger (54 [46-62] vs 57 [47-64] years, P < 0.001) and were more frequently privately insured (45.1 vs 39.4 %, P < 0.001). On average, the Bariatric more frequently underwent operative management, relative to Non-Bariatric (44.8 vs 29.7 %, P < 0.001). Following risk adjustment, among those surgically managed, Bariatric demonstrated lower odds of mortality (Adjusted Odds Ratio [AOR] 0.69, 95 % Confidence Interval [CI] 0.55-0.87) compared to Non-Bariatric. Bariatric also demonstrated lower odds of infectious and renal complications. Furthermore, the Bariatric cohort had lower costs, length of stay, and non-home discharge. Conclusions: Patients with prior bariatric surgery demonstrated a lower likelihood of mortality, decreased complications, and reduced resource utilization, relative to others. As the incidence of bariatric surgery continues to rise, future work is needed to minimize the incidence of SBO among these patients, especially in the current era of value-based healthcare.

Percutaneous cholecystostomy tube placement as a bridge to cholecystectomy for grade III acute cholecystitis: A national analysis.

Introduction: Percutaneous cholecystostomy (PCT) is an alternative to cholecystectomy (CCY) in high-risk surgical candidates with severe acute cholecystitis. A subset of these patients ultimately undergo delayed CCY. We therefore compared outcomes of delayed CCY in patients with grade III acute cholecystitis who received a PCT on index admission, to those who did not. Methods: Non-elective adult hospitalizations for grade III acute cholecystitis that underwent delayed CCY were identified in the 2016-2020 Nationwide Readmission Database. Patients who received a PCT during their index admission comprised the PCT group (others: Non-PCT). Outcomes were assessed for the CCY hospitalization. Entropy balancing was used to generate sample weights to adjust for differences in baseline characteristics. Regression models were created to evaluate the association between PCT and the outcomes of interest. Results: Of an estimated 13,782 patients, 13.3 % comprised PCT. Compared to Non-PCT, PCT were older (71.1 ± 13.1 vs 67.4 ± 15.3 years) and more commonly in the highest income quartile (22.5 vs 16.1 %, both p < 0.001). After risk adjustment, PCT was associated with reduced odds of respiratory (AOR 0.67, CI 0.54-0.83) and infectious (AOR 0.77, CI 0.62-0.96) complications after eventual CCY. Finally, PCT had comparable pLOS (ß +0.31, CI [-0.14, 0.77]) and operative hospitalization costs (ß $800, CI [-2300, +600]). Conclusion: In the present study, PCT was associated with decreased odds of perioperative complications and comparable resource utilization upon readmission CCY. Our findings suggest that PCT may be helpful in bridging patients with grade III acute cholecystitis to eventual CCY.

National outcomes of expedited discharge following esophagectomy for malignancy.

BACKGROUND: Expedited discharge following esophagectomy is controversial due to concerns for higher readmissions and financial burden. The present study aimed to evaluate the association of expedited discharge with hospitalization costs and unplanned readmissions following esophagectomy for malignant lesions. METHODS: Adults undergoing elective esophagectomy for cancer were identified in the 2014-2019 Nationwide Readmissions Database. Patients discharged by postoperative day 7 were considered Expedited and others as Routine. Patients who did not survive to discharge or had major perioperative complications were excluded. Multivariable regression models were constructed to assess association of expedited discharge with index hospitalization costs as well as 30- and 90-day non-elective readmissions. RESULTS: Of 9,886 patients who met study criteria, 34.6% comprised the Expedited cohort. After adjustment, female sex (adjusted odds ratio [AOR] 0.71, p = 0.001) and increasing Elixhauser Comorbidity Index (AOR 0.88/point, p<0.001) were associated with lower odds of expedited discharge, while laparoscopic (AOR 1.63, p<0.001, Ref: open) and robotic (AOR 1.67, p = 0.003, Ref: open) approach were linked to greater likelihood. Patients at centers in the highest-tertile of minimally invasive esophagectomy volume had increased odds of expedited discharge (AOR 1.52, p = 0.025, Ref: lowest-tertile). On multivariable analysis, expedited discharge was independently associated with an $8,300 reduction in hospitalization costs. Notably, expedited discharge was associated with similar odds of 30-day (AOR 1.10, p = 0.40) and 90-day (AOR 0.90, p = 0.70) unplanned readmissions. CONCLUSION: Expedited discharge after esophagectomy was associated with decreased costs and unaltered readmissions. Prospective studies are necessary to robustly evaluate whether expedited discharge is appropriate for select patients undergoing esophagectomy.

Anatomical and functional organization of cardiac fibers in the porcine cervical vagus nerve allows spatially selective efferent neuromodulation.

Cardiac disease progression reflects the dynamic interaction between adversely remodeled neurohumoral control systems and an abnormal cardiac substrate. Vagal nerve stimulation (VNS) is an attractive neuromodulatory option to dampen this dynamic interaction; however, it is limited by off-target effects. Spatially-selective VNS (sVNS) offers a promising solution to induce cardioprotection while mitigating off-target effects by specifically targeting pre-ganglionic parasympathetic efferent cardiac fibers. This approach also has the potential to enhance therapeutic outcomes by eliminating time-consuming titration required for optimal VNS. Recent studies have demonstrated the independent modulation of breathing rate, heart rate, and laryngeal contraction through sVNS. However, the spatial organization of afferent and efferent cardiac-related fibers within the vagus nerve remains unexplored. By using trial-and-error sVNS in vivo in combination with ex vivo micro-computed tomography fascicle tracing, we show the significant spatial separation of cardiac afferent and efferent fibers (179±55° SD microCT, p<0.05 and 200±137° SD, p<0.05 sVNS - degrees of separation across a cross-section of nerve) at the mid-cervical level. We also show that cardiac afferent fibers are located in proximity to pulmonary fibers consistent with recent findings of cardiopulmonary convergent neurons and circuits. We demonstrate the ability of sVNS to selectively elicit desired scalable heart rate decrease without stimulating afferent-related reflexes. By elucidating the spatial organization of cardiac-related fibers within the vagus nerve, our findings pave the way for more targeted neuromodulation, thereby reducing off-target effects and eliminating the need for titration. This, in turn, will enhance the precision and efficacy of VNS therapy in treating cardiac pathology, allowing for improved therapeutic efficacy.

National Trends and Clinical Outcomes after Scooter Injury in the US: 2016 to 2020.

BACKGROUND: In recent years, the adoption of electric scooters has been accompanied by a surge of scooter-related injuries in the US, raising concerns for their severity and associated healthcare costs. This study aimed to assess temporal trends and outcomes of scooter-related hospital admissions compared with bicycle-related hospitalizations. STUDY DESIGN: This was a retrospective cohort study using the 2016 to 2020 National Inpatient Sample for patients younger than 65 years who were hospitalized after bicycle- and scooter-related injuries. The Trauma Mortality Prediction Model was used to quantify injury severity. The primary outcomes of interest were temporal trends of micromobility injuries. In-hospital mortality, rates of long bone fracture, traumatic brain injury, paralysis, length of stay, hospitalization costs, and nonhome discharge were secondarily assessed. RESULTS: Among 92,815 patients included in the study, 6,125 (6.6%) had scooter-related injuries. Compared with patients with bicycle-related injuries, patients with scooter-related injuries were more commonly younger than 18 years (26.7% vs 16.4%, p < 0.001) and frequently underwent major operations (55.8% vs 48.1%, p < 0.001). After risk adjustment, scooter-related injuries were associated with greater risks of long bone fracture (adjusted odds ratio 1.40, 95% CI 1.15 to 1.70) and paralysis (adjusted odds ratio 2.06, 95% CI 1.16 to 3.69) compared with bicycle-related injuries. Additionally, patients with bicycle- or scooter-related injuries had comparable index hospitalization durations of stay and costs. CONCLUSIONS: The prevalence and severity of scooter-related injuries have significantly increased in the US, thereby attributing to a substantial cost burden on the healthcare system. Multidisciplinary efforts to inform safety policies and enact targeted interventions are warranted to reduce scooter-related injuries.

Center-Level Variation in Hospitalization Costs of Transcatheter Aortic Valve Replacement.

BACKGROUND: Using a nationally representative database, the present study evaluated the degree of center-level variation in the cost of transcatheter aortic valve replacement (TAVR). METHODS: All adults undergoing elective, isolated TAVR were identified in the 2016 to 2018 Nationwide Readmissions Database. Multilevel mixed-effects models were used to identify patient and hospital characteristics associated with hospitalization costs. The random intercept for each hospital was generated and considered to be the baseline cost attributable to care at each center. Hospitals in the highest decile of baseline costs were classified as high-cost hospitals. The association of high-cost hospital status with in-hospital mortality and perioperative complications was subsequently assessed. RESULTS: An estimated 119,492 patients, with a mean age of 80 years and a 45.9% prevalence of female sex, met the study criteria. Analysis of random intercepts indicated that 54.3% of variability in costs was attributable to interhospital differences rather than patient factors. Perioperative respiratory failure, neurologic complications, and acute kidney injury were associated with increased episodic expenditure but did not explain the observed center-level variation. The baseline cost associated with each hospital ranged from -$26,000 to $162,000. Notably, high-cost hospital status was not linked to annual TAVR caseload or to odds of mortality (P = .83), acute kidney injury (P = .18), respiratory failure (P = .32), or neurologic complications (P = .55). CONCLUSIONS: The present analysis identified significant variation in the cost of TAVR, which was largely attributable to center-level rather than patient factors. Hospital TAVR volume and occurrence of complications were not drivers of the observed variation.

Center-Level Variation in Failure to Rescue After Pediatric Cardiac Surgery.

BACKGROUND: Although failure to rescue (FTR) is increasingly recognized as a quality metric, studies in congenital cardiac surgery remain sparse. Within a national cohort of children undergoing cardiac operations, we characterized the presence of center-level variation in FTR and hypothesized a strong association with mortality but not complications. METHODS: All children undergoing congenital cardiac operations were identified in the 2013 to 2019 Nationwide Readmissions Database. FTR was defined as in-hospital death after cardiac arrest, ventricular tachycardia/fibrillation, prolonged mechanical ventilation, pneumonia, stroke, venous thromboembolism, or sepsis, among other complications. Hierarchical models were used to generate hospital-specific, risk-adjusted rates of mortality, complications, and FTR. Centers in the highest decile of FTR were identified and compared with others. RESULTS: Of an estimated 74,070 patients, 1.9% died before discharge, at least 1 perioperative complication developed in 43.0%, and 4.1% experienced FTR. After multilevel modeling, decreasing age, nonelective admission, and increasing operative complexity were associated with greater odds of FTR. Variations in overall mortality and FTR exhibited a strong, positive relationship (r = 0.97), whereas mortality and complications had a negligible association (r = -0.02). Compared with others, patients at centers with high rates of FTR had similar distributions of age, sex, chronic conditions, and operative complexity. CONCLUSIONS: In the present study, center-level variations in mortality were more strongly explained by differences in FTR than complications. Our findings suggest the utility of FTR as a quality metric for congenital heart surgery, although further study is needed to develop a widely accepted definition and appropriate risk-adjustment models.

Association of prior bariatric surgery with financial and clinical outcomes of acute myocardial infarction.

BACKGROUND: Superior clinical outcomes after hospitalization for cardiovascular-related disease such as acute heart failure have been linked with prior history of bariatric surgery, but similar analyses in acute myocardial infarction (MI) are currently limited. OBJECTIVE: This work examines clinical outcomes and resource utilization in patients with acute MI hospitalizations with a prior history of bariatric surgery. SETTING: Academic university-affiliated hospital in the United States. METHODS: All adult patients with hospitalizations with a primary diagnosis of acute MI were queried using the 2016-2020 Nationwide Readmissions Database. The study population was comprised of patients with an International Classification of Diseases, Tenth Revision (ICD-10) diagnosis code for obesity (body mass index ≥35 kg/m2) as well as those with a prior history of bariatric surgery regardless of their body mass index status. Comparison was made between those with a prior history of bariatric surgery and those without. Univariate analysis and multivariate regression models were used to examine the association between bariatric surgery and outcomes of interest, which included in-hospital mortality, medical complications, and resource utilization. RESULTS: Of an estimated 2,736,606 hospitalizations for acute MI, 296,902 patients (10.8%) had a diagnosis of obesity and/or a prior history of bariatric surgery. The bariatric cohort was more frequently female and had a lower prevalence of congestive heart failure, chronic lung disease, diabetes, and electrolyte derangements than the nonbariatric cohort. After risk adjustment, prior history of bariatric surgery was associated with significantly lower odds of in-hospital mortality, cardiogenic shock, and acute kidney injury. Additionally, prior history of bariatric surgery was linked to a decreased duration of hospital stay and lower hospitalization costs as well as lower odds of nonhome discharge. CONCLUSION: Among acute MI patients with obesity, prior history of bariatric surgery was associated with decreased odds of in-hospital mortality, improved clinical outcomes, and lower resource utilization. Expansion of bariatric surgery programs may provide improved access to a medical intervention that is intertwined with cardiovascular health.

The vagus nerve in cardiovascular physiology and pathophysiology: From evolutionary insights to clinical medicine.

The parasympathetic nervous system via the vagus nerve exerts profound influence over the heart. Together with the sympathetic nervous system, the parasympathetic nervous system is responsible for fine-tuned regulation of all aspects of cardiovascular function, including heart rate, rhythm, contractility, and blood pressure. In this review, we highlight vagal efferent and afferent innervation of the heart, with a focus on insights from comparative biology and advances in understanding the molecular and genetic diversity of vagal neurons, as well as interoception, parasympathetic dysfunction in heart disease, and the therapeutic potential of targeting the parasympathetic nervous system in cardiovascular disease.

Care fragmentation is associated with increased mortality after ileostomy creation.

BACKGROUND: Ileostomy is the mainstay treatment option for various gastrointestinal conditions. Given the increased risk of post-discharge complications and high readmission rates that can be further aggravated by receiving care at different facilities (care fragmentation), further examination is necessary. We thus used a national cohort to explore the associations of care fragmentation among ileostomy patients experiencing adverse outcomes and increased hospitalization expenditures. METHODS: All adult hospitalizations for ileostomy were tabulated from the 2016 to 2020 Nationwide Readmissions Database. Those readmitted within 90 days after discharge were included for analysis. Patients treated at a different facility than the original location where the index ileostomy was performed were categorized into the care-fragmented cohort. Multivariable regressions were developed to characterize the association of the care-fragmented cohort with postoperative outcomes, readmissions, and expenditures. RESULTS: Of 52,254 patients with ileostomy creation hospitalizations with 90-day nonelective readmission, 9,045 (17.3%) experienced care fragmentation. Following risk adjustment, those experiencing care fragmentation faced increased odds of mortality (adjusted odds ratio 1.81, 95% confidence interval 1.54-2.12), cardiac (adjusted odds ratio 1.63, 95% confidence interval 1.42-1.85), respiratory (adjusted odds ratio 1.71, 95% confidence interval 1.53-1.91), infectious (adjusted odds ratio 1.33, 95% confidence interval 1.23-1.43), and thromboembolic (adjusted odds ratio 1.28, 95% confidence interval 1.13-1.45) complications. Furthermore, patients experiencing care fragmentation were more likely to have increased hospitalization costs ($1,700, 95% confidence interval 0.8-2.5). CONCLUSION: Care fragmentation in ileostomy patients demonstrated an increased risk for mortality, postoperative complications, and increased hospitalization expenses. To mitigate risks for adverse outcomes, future studies should evaluate the impacts of inter-hospital communication with the goal of improving care continuity and optimizing healthcare delivery for care-fragmented populations.

Machine Learning Based Prediction of Postoperative Pancreatic Fistula Following Pancreaticoduodenectomy.

OBJECTIVE: To develop a novel machine learning (ML) model to predict clinically relevant postoperative pancreatic fistula (CR-POPF) following pancreaticoduodenectomy (PD). SUMMARY BACKGROUND DATA: Accurate prognostication of CR-POPF may allow for risk stratification and adaptive treatment strategies for potential PD candidates. However, antecedent models, such as the modified Fistula Risk Score (mFRS), are limited by poor discrimination and calibration. METHODS: All records entailing PD within the 2014-2018 ACS NSQIP were identified. Additionally, patients undergoing PD at our institution between 2013 and 2021 were queried from our local data repository. An eXtreme Gradient Boosting (XGBoost) model was developed to estimate the risk of CR-POPF using data from the ACS NSQIP and evaluated using institutional data. Model discrimination was estimated using the area under the receiver operating characteristic (AUROC) and precision recall curve (AUPRC). RESULTS: Overall, 12,281 and 445 patients undergoing PD were identified within the 2014-2018 ACS NSQIP and our institutional registry, respectively. Application of the XGBoost and mFRS scores to the internal validation dataset revealed that the former model had significantly greater AUROC (0.72 vs. 0.68, P<0.001) and AUPRC (0.22 vs. 0.18, P<0.001). Within the external validation dataset, the XGBoost model remained superior to the mFRS with an AUROC of 0.79 (95% CI 0.74-0.84) versus 0.75 (95% CI 0.70-0.80, P<0.001). In addition, AUPRC was higher for the XGBoost model, compared to the mFRS. CONCLUSIONS: Our novel ML model consistently outperformed the previously validated mFRS within internal and external validation cohorts, thereby demonstrating its generalizability and utility for enhancing prediction of CR-POPF.

Vagal Nerve Stimulation Reduces Ventricular Arrhythmias and Mitigates Adverse Neural Cardiac Remodeling Post-Myocardial Infarction.

This study sought to evaluate the impact of chronic vagal nerve stimulation (cVNS) on cardiac and extracardiac neural structure/function after myocardial infarction (MI). Groups were control, MI, and MI + cVNS; cVNS was started 2 days post-MI. Terminal experiments were performed 6 weeks post-MI. MI impaired left ventricular mechanical function, evoked anisotropic electrical conduction, increased susceptibility to ventricular tachycardia and fibrillation, and altered neuronal and glial phenotypes in the stellate and dorsal root ganglia, including glial activation. cVNS improved cardiac mechanical function and reduced ventricular tachycardia/ventricular fibrillation post-MI, partly by stabilizing activation/repolarization in the border zone. MI-associated extracardiac neural remodeling, particularly glial activation, was mitigated with cVNS.

Impact of surgeon specialty on clinical outcomes following esophagectomy for cancer.

BACKGROUND: The impact of surgeon and hospital operative volume on esophagectomy outcomes is well-described; however, studies examining the influence of surgeon specialty remain limited. Therefore, we evaluated the impact of surgeon specialty on short-term outcomes following esophagectomy for cancer. METHODS: The 2016-2019 American College of Surgeons National Surgical Quality Improvement Project (ACS NSQIP) was queried to identify all patients undergoing esophagectomy for esophageal cancer. Surgeon specialty was categorized as general (GS) or thoracic (TS). Entropy balancing was used to generate sample weights that adjust for baseline differences between GS and TS patients. Weights were subsequently applied to multivariable linear and logistic regressions, which were used to evaluate the independent association of surgeon specialty with 30-day mortality, complications, and postoperative length of stay. RESULTS: Of 2657 esophagectomies included for analysis, 54.1% were performed by TS. Both groups had similar distributions of age, sex, and body mass index. TS patients more frequently underwent transthoracic esophagectomy, while GS patients more commonly received minimally invasive surgery. After adjustment, surgeon specialty was not associated with altered odds of 30-day mortality (adjusted odds ratio [AOR] 1.10 p = 0.73) or anastomotic leak (AOR 0.87, p = 0.33). However, TS patients exhibited a 40-min reduction in operative duration and faced greater odds of perioperative transfusion, relative to GS. CONCLUSION: Among ACS NSQIP participating centers, surgeon specialty influenced operative duration and blood product utilization, but not mortality and anastomotic leak. Our results support the relative safety of esophagectomy performed by select GS and TS.

Association of Hospital Volume and Outcomes Following Off-Pump Coronary Artery Bypass Grafting.

BACKGROUND: Off-pump coronary artery bypass grafting (OPCAB) has been used to mitigate the negative systemic effects of cardiopulmonary bypass. Recent consortium and single-institution studies suggest an association between operator experience and long-term survival. We thus aimed to ascertain the relationship between institutional OPCAB volume and outcomes using a contemporary nationwide all-payer database. METHODS: Adult admissions for elective isolated OPCAB were identified from the 2016-2019 Nationwide Readmissions Database. The primary outcome was major adverse events (MAE), defined as a composite of mortality, reoperation, prolonged mechanical ventilation, acute kidney injury requiring dialysis, or perioperative stroke during the index hospitalisation. Secondary outcomes included temporal trends, postoperative length of stay (pLOS), hospitalisation costs, non-home discharge, and 30-day readmission rate. High-volume hospitals (HVH) were defined to have annual caseloads >35 based on cubic spline analysis. RESULTS: Of an estimated 41,154 patients, 59.9% were treated at HVH. The proportion of coronary artery bypass grafting operations that were OPCAB significantly decreased from 21.1% in 2016 to 18.3% in 2019. After adjustment, HVH status was associated with lower adjusted odds of MAE (adjusted odds ratio [AOR] 0.78, 95% confidence interval [CI] 0.70-0.88), compared to others. HVH were also associated with shorter pLOS (ß -0.10, 95% -0.13, -0.07), reduced costs (ß -US$4,900, - US$6,300, - US$3,600), non-home discharge (AOR 0.54, 95% CI 0.45-0.64), and 30-day readmission (AOR 0.86, 95% CI 0.77-0.96). CONCLUSIONS: Our results suggest that OPCAB requires a distinct set of surgical expertise and institutional aptitude. As a result, centralisation of care to centres of excellence should be considered.